1. Neuroscience
  2. Structural Biology and Molecular Biophysics
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Molecular basis for functional connectivity between the voltage sensor and the selectivity filter gate in Shaker K+ channels

  1. Carlos A Z Bassetto Jnr
  2. João Luis Carvalho-de-Souza
  3. Francisco Bezanilla  Is a corresponding author
  1. University of Chicago, United States
  2. University of Arizona, United States
Research Article
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Cite this article as: eLife 2021;10:e63077 doi: 10.7554/eLife.63077


In Shaker K+ channels, the S4-S5 linker couples the voltage sensor (VSD) and pore domain (PD). Another coupling mechanism is revealed using two W434F-containing channels: L361R:W434F and L366H:W434F. In L361R:W434F, W434F affects the L361R VSD seen as a shallower Q-V curve that crosses the G-V. In L366H:W434F, L366H relieves the W434F effect converting a non-conductive channel in a conductive one. We report a chain of residues connecting the VSD (S4) to the selectivity filter (SF) in the PD of an adjacent subunit as the molecular basis for voltage-sensor selectivity filter gate (VS-SF) coupling. Single alanine substitutions in this region (L409A, S411A, S412A or F433A) are enough to disrupt the VS-SF coupling, shown by the absence of Q-V and G-V crossing in L361R:W434F mutant and by the lack of ionic conduction in the L366H:W434F mutant. This residue chain defines a new coupling between the VSD and the PD in voltage-gated channels.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

Article and author information

Author details

  1. Carlos A Z Bassetto Jnr

    Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. João Luis Carvalho-de-Souza

    Department of Anesthesiology, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Francisco Bezanilla

    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6663-7931


National Institutes of Health (R01-GM030376)

  • Francisco Bezanilla

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institution of animal care and use committee (IACUC) protocols (#71745) of the University of Chicago.

Reviewing Editor

  1. Baron Chanda, Washington University in St. Louis, United States

Publication history

  1. Received: September 14, 2020
  2. Accepted: February 22, 2021
  3. Accepted Manuscript published: February 23, 2021 (version 1)
  4. Version of Record published: March 8, 2021 (version 2)


© 2021, Bassetto et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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